TY - JOUR
T1 - Derivation of a new model of lung adenocarcinoma using canine lung cancer organoids for translational research in pulmonary medicine
AU - Shiota Sato, Yomogi
AU - Elbadawy, Mohamed
AU - Suzuki, Kazuhiko
AU - Tsunedomi, Ryouichi
AU - Nagano, Hiroaki
AU - Ishihara, Yusuke
AU - Yamamoto, Haru
AU - Azakami, Daigo
AU - Uchide, Tsuyoshi
AU - Fukushima, Ryuji
AU - Tanaka, Ryo
AU - Yoshida, Tomohiko
AU - Mori, Takuya
AU - Abugomaa, Amira
AU - Kaneda, Masahiro
AU - Yamawaki, Hideyuki
AU - Shinohara, Yuta
AU - Aboubakr, Mohamed
AU - El-Asrag, Mohamed E.
AU - Usui, Tatsuya
AU - Sasaki, Kazuaki
N1 - Copyright © 2023 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).
PY - 2023/9
Y1 - 2023/9
N2 - Canine primary lung cancer (cPLC) is a rare malignant tumor in dogs, and exhibits poor prognosis. Effective therapeutic drugs against cPLC have not been established yet. Also, cPLC resembles human lung cancer in histopathological characteristics and gene expression profiles and thus could be an important research model for this disease. Three-dimensional organoid culture is known to recapitulate the tissue dynamics in vivo. We, therefore, tried to generate cPLC organoids (cPLCO) for analyzing the profiles of cPLC. After samples from cPLC and the corresponding normal lung tissue were collected, cPLCO were successfully generated, which recapitulated the tissue architecture of cPLC, expressed lung adenocarcinoma marker (TTF1), and exhibited tumorigenesis in vivo. The sensitivity of cPLCO to anti-cancer drugs was different among strains. RNA-sequencing analysis showed significantly upregulated 11 genes in cPLCO compared with canine normal lung organoids (cNLO). Moreover, cPLCO were enriched with the MEK-signaling pathway compared with cNLO. The MEK inhibitor, trametinib decreased the viability of several strains of cPLCO and inhibited the growth of cPLC xenografts. Collectively, our established cPLCO model might be a useful tool for identifying novel biomarkers for cPLC and a new research model for dog and human lung cancer.
AB - Canine primary lung cancer (cPLC) is a rare malignant tumor in dogs, and exhibits poor prognosis. Effective therapeutic drugs against cPLC have not been established yet. Also, cPLC resembles human lung cancer in histopathological characteristics and gene expression profiles and thus could be an important research model for this disease. Three-dimensional organoid culture is known to recapitulate the tissue dynamics in vivo. We, therefore, tried to generate cPLC organoids (cPLCO) for analyzing the profiles of cPLC. After samples from cPLC and the corresponding normal lung tissue were collected, cPLCO were successfully generated, which recapitulated the tissue architecture of cPLC, expressed lung adenocarcinoma marker (TTF1), and exhibited tumorigenesis in vivo. The sensitivity of cPLCO to anti-cancer drugs was different among strains. RNA-sequencing analysis showed significantly upregulated 11 genes in cPLCO compared with canine normal lung organoids (cNLO). Moreover, cPLCO were enriched with the MEK-signaling pathway compared with cNLO. The MEK inhibitor, trametinib decreased the viability of several strains of cPLCO and inhibited the growth of cPLC xenografts. Collectively, our established cPLCO model might be a useful tool for identifying novel biomarkers for cPLC and a new research model for dog and human lung cancer.
KW - Humans
KW - Dogs
KW - Animals
KW - Translational Research, Biomedical
KW - Pulmonary Medicine
KW - Adenocarcinoma of Lung/drug therapy
KW - Lung Neoplasms/drug therapy
KW - Organoids
KW - Mitogen-Activated Protein Kinase Kinases/metabolism
UR - https://www.sciencedirect.com/science/article/pii/S0753332223008703
U2 - 10.1016/j.biopha.2023.115079
DO - 10.1016/j.biopha.2023.115079
M3 - Article
C2 - 37413906
SN - 0753-3322
VL - 165
JO - Biomedicine & Pharmacotherapy
JF - Biomedicine & Pharmacotherapy
M1 - 115079
ER -